DESCRIPTION: This twice revised application proposes to study the response of osteoblasts to mechanical strains. A new and novel device will be used for mechanically deforming a flexible substrate on which osteoblast cultures are attached in three distinct phases of development, proliferation, differentiation and phenotypic expression, and extracellular matrix mineralization. The mechanisms by which the mechanical deformations modulate osteoblastic activity will be studied as a function of strain amplitudes, frequency, duty cycle, and duration. DNA synthesis, protein synthesis and accumulation, gene expression of specific extracellular matrix proteins, and rates of extracellular matrix mineralization will be measured. In addition, intracellular architectural response to the major cytoskeletal elements will be examined.